 So doing things with simple methods looks great as I'm showing you here in this movie, but the point is This simplification has to come from somewhere. I can't just invent things out of thin air. So why does this work? Well, it works because we're cheating and the cool thing is in real life. You're occasionally allowed to cheat So remember the water molecule We don't really have that many things to chew in water if we make this simple You could argue that we have the charge on the oxygen and no matter what charge I put on the oxygen I'm gonna need to put half that charge of the opposite sign on the hydrogen So that's really just one number I can tune how the charge is distributed between the oxygens and the hydrogens The first approximation I will say that the angle and the bonds here that I'll take those from quantum chemistry So I'm not really gonna change those The other part is that we're gonna need some sort of parameter describing the repulsion between this That is if two atoms get close to each other, how much are they repelling each other in? Principle that is two parameters one for the oxygens and one for the hydrogens But you will have to trust me when I say this if you were to draw and Water molecule a real way based on the radius of the atom It would look completely bonkers and that's why we don't do it because it would look rough in this way This would be the oxygen and this would be one hydrogens and this would be the other hydrogens So you can probably come up with a reasonably easy Approximation here and if we just erase those hydrogens from the lanard Jones interactions the thunder balls I'll get back to those in a second so that it's pretty much just one sphere with one radius That's one parameter and we combine that with the distribution of charge. That is two parameters. I Can in principle set these two parameters to anything I want. So what should I set it based on? Well, I look at water and there are two very simple things with water I know what the density of water should be and I know roughly how expensive it should be to say boil water at the heat of Apparization and I can just change these parameters to make sure that they fit the experimental properties of water It's a horrible way of cheating and of course the reason this works is that quantum chemistry would get the same results But from fundamental first principles here I'm skipping over all that and just tuning it to fit the experiment But if that works, then I'm able to reproduce the diffusion coefficient of water as I'm doing in this movie works great And I'm able to do this orders of magnitude cheaper than I could do with quantum chemistry. So the pretty cool approximation Who came up with that approximation? well There were a number of scientists involved in this There's a long long long story in this field and unfortunately I won't have time to take you through all of it, but it started out the engineer lifts on slab in Israel and coming very much from Polymer physics Sorry, I might even have said it and The situation in Polymer physics is that people started using something called semi-empiric parametrization That sounds difficult. It's not really the first principle once with that would be the quantum chemistry The fully empiric parameter is that would be if I just tune everything to fit experiments and I didn't do that here Right, I took the bond lengths from quantum chemistry I took the angles from quantum chemistry at some points you're going to see that we take charges from quantum chemistry So I kind of use a little bit of quantum chemistry And then I combine that with parameterizing it to fit experiments and that's why we call it semi-empiric methods These methods have become immensely popular the last few decades The first people to come up with this was actually, well, there was Schneer, Lifson and Ari Warshall in particular And based on these methods Ari and a few other colleagues were able to determine very detailed models of large molecules and simes where they use quantum chemistry for a small part in the middle and then the semi-empiric models outside of it And for that work they were rewarded with a Nobel Prize in chemistry in 2013 Almost any high impact paper you read in biology today if it's a new structure or something They frequently include a bit of simulation which is kind of fascinating because only 20 years ago this was something very esoteric and theoretical physics We're not going to start doing simulations quite yet But we will have to look into a little bit about the interactions and how we model interactions in proteins Because that's going to be super useful when we start revisiting protein structure next week Simple